Stereo Chemistry

3 3 2 1 3 2 2 1 2 1 1 2 2 1 1

25

44

5 4 4 4 5 4 4 4 5 3 3 3 3 2.5 2.5

56

100

0

20

40

60

80

100

120

Mua

tan

Form

al

Arah

Elekt

ron

Strukt

ur R

eson

ansi

Hibrid

isasi

Mua

tan

Form

al

Arah

Elekt

ron

Strukt

ur R

eson

ansi

Hibrid

isasi

Basa

Lewis

Efek

Keelek

trone

gatifa

n da

n uk

uran

Efek

Indu

ksi

Efek

Hibrid

isasi

Nama

Gugus

Jeni

s Ika

tan

Hibrid

isasi

Total

Nilai

Konsep

Nila

i

Nilai Rata2 Mahasiswa

Nilai Acuan

Persentase Keberhasilan

66 6762

22

5753

42

25

43 43

35

70 67

48

32

44 44

0

10

20

30

40

50

60

70

80

Mua

tan

Form

al

Stru

ktur

Res

onan

si

Mua

tan

Form

al

Stru

ktur

Res

onan

si

Basa

Lew

is

Efek

Indu

ksi

Nam

a G

ugus

Hib

ridis

asi

Nila

i

Persentase Keberhasilan

OPTICAL ACTIVITYOPTICAL ACTIVITY

PLANE-POLARIZED LIGHT

.

PLANE-POLARIZED LIGHT BEAMPLANE-POLARIZED LIGHT BEAM

unpolarizedbeam

wavelength

=c

frequency ( )

c = speed of light

polarized beam

All sine waves (rays) in the beam aligned in same plane.

Sine wavesare not alignedin the sameplane.

NOT PLANE-POLARIZED

ENDVIEWSIDE

VIEW

singleray orphoton

A beam is a collectionof these rays.

Optically ActiveOptically Active

• Refers to molecules that interact with plane-polarized light

Jean Baptiste Biot French Physicist - 1815

He discovered that some natural substances (glucose, nicotine, sucrose) rotate the plane of plane-polarized light and that others did not.

Dextrorotatory

Rotates the plane of plane-polarized lightto the right.

(+)- d-

Levorotatory

Rotates the plane of plane-polarized lightto the left.

(-)- l-

TYPES OF OPTICAL ACTIVITYTYPES OF OPTICAL ACTIVITYnew older

new older

[]D = cl

Specific Rotation []D

= observed rotation

c = concentration ( g/mL )

l = length of cell ( dm )

D = yellow light from sodium lamp

t = temperature ( Celsius )

t

Specific rotation calculated in this way is a physicalproperty of an optically active substance.

This equation correctsfor differences in celllength and concentration.

You always get the same

[]D tvalue of

The PolarimeterThe Polarimeter

chemistrynerd

sample cell

polarizer

Na lamp

plane isrotated analyzer

plane-polarizedlight

observedrotation

00000

rotate to null

STEREOISOMERSSTEREOISOMERS

ENANTIOMERS

PASTEUR’S DISCOVERY

Louis Pasteur 1848 Sorbonne, Paris

HOOC CH CH COOH

OH OH

OOC CH CH COO

OH OH

NH4Na ++2-

tartaric acid sodium ammonium tartrate( found in wine must )

Pasteur crystallized thissubstance on a cold day.

(+) (-)Louis Pasteur separated these and gave them to Biot to measure.

Biot’s results :

mirrorimages

Crystals of Sodium Ammonium TartrateCrystals of Sodium Ammonium Tartrate

hemihedral facesPasteur found twodifferent crystals.

EnantiomersEnantiomers

W

CX

ZY

W

CXY

Z

non-superimposable mirror images

Pasteur decided that the molecules that made the crystals,just as the crystals themselves, must be mirror images. Each crystal must contain a single type of enantiomer.

(also called optical isomers)

Pasteur’s hypothesis eventually led to the discoverythat tetravalent carbon atoms are tetrahedral.

Only tetrahedral geometry can lead to mirror imagemolecules:

Square planar, square pyrimidal or trigonal pyramidwill not work:

C

C C

tetrahedralcarbon

C C C

Van’t Hoff andLeBel (1874)

ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS

W

CX

ZY

W

CXY

Z

(+)-nno (-)-nno

dextrorotatory levorotatory

Enantiomers

ALL OTHER PHYSICAL PROPERTIES ARE THE SAME

H COOHH

OHOH

HOOCHOOC HH COOH

OHOH

H HCOOH

OHOH

HOOC

meso

enantiomers

(as a minor component)ALSO FOUND

more about thiscompound later

H COOHH

OHOH

HOOCHOOC HH COOH

OHOH

H HCOOH

OHOH

HOOC

meso

enantiomers(+)-tartaric acid (-)-tartaric acid

TARTARIC ACIDTARTARIC ACIDfrom fermentation of wine

[]D = 0

meso -tartaric acid

Enantiomers

TARTARIC ACIDTARTARIC ACID

(-) - tartaric acid (+) - tartaric acid

[]D = -12.0o []D = +12.0o

mp 168 - 170o mp 168 - 170o

solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL etherinsoluble CHCl3


d = 1.758 g/mL d = 1.758 g/mL

meso - tartaric acid

mp 140o

d = 1.666 g/mL

solubility of 1 g 0.94 mL H2O

[]D = 0o

insoluble CHCl3

RACEMIC MIXTURERACEMIC MIXTURE

an equimolar (50/50) mixture of enantiomers

[]D = 0o

the effect of each molecule is cancelled out by its enantiomer

CHIRALITY, SYMMETRY PLANES CHIRALITY, SYMMETRY PLANES AND ENANTIOMERSAND ENANTIOMERS

PLANES OF SYMMETRYPLANES OF SYMMETRY

plane ofsymmetry

mirrorplane

A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY - ALSO CALLED A MIRROR PLANE- ALSO CALLED A MIRROR PLANE

IF AN OBJECT HAS A PLANE OF SYMMETRY, IF AN OBJECT HAS A PLANE OF SYMMETRY, ITS MIRROR IMAGE WILL BE IDENTICALITS MIRROR IMAGE WILL BE IDENTICAL

IDENTICAL MIRROR IMAGES WILL SUPERIMPOSESUPERIMPOSE(MATCH EXACTLY WHEN PLACED ON TOP OF EACH OTHER)

CHIRALITYCHIRALITY

no symmetry

CHIRALCHIRALAn object without symmetry is

The mirror imageof a chiral object isdifferent and will notsuperimpose on the original object.

OBJECTS WHICH ARE CHIRALHAVE A SENSE OF “HANDEDNESS”AND EXIST IN TWO FORMS

An object with symmetry is ACHIRALACHIRAL ( not chiral).

The mirror image of an achiral object is identical and will superimpose on the original object.

plane of symmetry

ENANTIOMERSENANTIOMERS

STEREOISOMERS

BrFH

Cl Cl

HBrF

HFBr

Cl

ENANTIOMERSENANTIOMERSnon-superimposable mirror images

rotate

this moleculeis chiral

note that the fluorineand bromine have beeninterchanged in theenantiomer

do interchanges in class

STEREOISOMERSSTEREOISOMERS

ENANTIOMERS are a type of STEREOISOMER

Stereoisomers are the same constitutional isomer,but have a difference in the way they are arrangedin three-dimensional space at one or more of theiratoms.

and remember …...


W

CX

ZY

W

CXY

Z

(+)-nno (-)-nno


Enantiomers


STEREOGENIC CARBON ATOMSSTEREOGENIC CARBON ATOMS

STEREOCENTERSSTEREOCENTERS

One of the ways a molecule can be chiral is to have astereocenter.

A stereocenter is an atom, or a group of atoms, that can potentially cause a molecule to be chiral.

stereocenters - cangive rise to chirality

BrFH

Cl

STEREOGENIC CARBONSSTEREOGENIC CARBONS

A stereogenic carbon is tetrahedral and has four different groups attached.

stereocenterThis is one type of ….

…. others are possible

( called “chiral carbons” in older literature )

HFClBr

ACHIRALACHIRAL

TWO IDENTICAL GROUPS RENDERS ATETRAHEDRAL CARBON ACHIRAL

F

BrClCl

ClClBr

F

The plane of the paper is a plane of symmetry

FClBr

ONE PAIR OF ATOMS ATTACHED TO A TETRAHEDRALCARBON IS IN A PLANE PERPENDICULAR TO THE OTHER PAIR

Look at yourmodel set !

plane 1

plane 2

FClBr

Cl

ClBr

F F

Br

Cl Cl

plane ofsymmetry

TWO VIEWS OF THE PLANE OF SYMMETRY

side view

edgeview

FClBr

Cl

BrClCl

ClClBr

Cl

A CARBON ATOM WITH THREE SIMILARGROUPS IS ALSO ACHIRAL …..

ACHIRALACHIRAL

ClBr

Cl

ClBrBr

Cl Cl

plane ofsymmetry

side view edge view

Cl Cl

CONFIGURATIONCONFIGURATION

ABSOLUTE CONFIGURATION ( R / S )

CONFIGURATIONCONFIGURATION

The three dimensional arrangement of the groups attached to an atom

Stereoisomers differ in the configuration at one ormore of their atoms.

2

CONFIGURATIONCONFIGURATION - relates to the three dimensionalsense of attachment for groups attached to a chiralatom or group of atoms (i.e., attached to a stereocenter).

clockwise counterclockwise

(rectus) (sinister)

view with substituentof lowestpriority inback

1 2

4

3

C C

1

4

3

R S

Enantiomers are assigned a CONFIGURATIONCONFIGURATIONusing the same priority rules we developed for E/Z stereoisomers.

1. Higher atomic number has higher priority.

2. If priority cannot be decided based on the first atom attached move to the next atom, following the path having the highest prioity atom.

3. Expand multiple bonds by replicating the atoms attached to each end of the bond.

SPECIFICATION OF CONFIGURATIONSPECIFICATION OF CONFIGURATION

SEQUENCE RULESEQUENCE RULECAHN-INGOLD-PRELOG

Cahn-Ingold-Prelog Cahn-Ingold-Prelog RR,,SS-Nomenclature-Nomenclature

Label all substituents at stereocenter, starting at Label all substituents at stereocenter, starting at point of attachment, according to the point of attachment, according to the sequence sequence rulesrules in order of in order of decreasingdecreasing priority: priority: aa, , bb, , cc, , dd (note color scheme). Look down C-(note color scheme). Look down C-d d bond:bond:

aa, , bb, , cc clockwise : clockwise : RR

aa, , bb, , cc counterclockwise : counterclockwise : SS

CC

aa

dd

bb

cc

Naming Enantiomers

RR

Cahn-Ingold-Prelog19661966

2. If same priority at first atom: Go to 2. If same priority at first atom: Go to first first point of difference.point of difference.

1. Order by 1. Order by atomic numberatomic number, i.e. H = 1, , i.e. H = 1, lowest. lowest.

--CCHH22CCHH22SSHH --CCHH22CCHH22SSCCHH33‹‹--CCHH22CCHH33 --CCCCHH33

CCHH33

HH‹‹

--CCHH22CCHH22OOHH --CCHHCCHH33

CCHH33

‹‹ --CCHHCCHH33

DD

‹‹-C-CHH22CCBrBr33

CC

HH

CHCH33

BrBrII

ccaa

bb

dd

NN ::**RR

Sequence Rules

dd

Exception: lone pair, Exception: lone pair,

# “zero”. E.g., amines:# “zero”. E.g., amines:

3. Multiple bonds: Add 3. Multiple bonds: Add double or triple double or triple representationsrepresentations of atoms at the respective of atoms at the respective other endother end of the multiple bond. of the multiple bond.

CC CC CC CC

CC CC

CC CC

HH HH

CC CCHHHH

CCOO

HH OOCCOOCCHH

NNCC CC NN

NN

CCNN

CC

CC CCCC CC

Procedure for Assignment of R, S

Fischer Projection:Fischer Projection: A flat stencil A flat stencil

BrBr HH

CCCCHH33CCHH22CHCH33

HH

BrBr

CCHH33CCHH22CHCH33

HH

BrBr

Eyes in the Eyes in the plane of the plane of the boardboard

Depending on your starting dashed-wedged Depending on your starting dashed-wedged line structure, line structure, severalseveral Fischer projections are Fischer projections are possible for the possible for the samesame molecule. molecule.

Fischer Projections

Rules for handling Fischer projections:Rules for handling Fischer projections:

1. 1. Don’t rotateDon’t rotate. .

2. The 2. The mutualmutual exchangeexchange of any pair gives the of any pair gives the otherother enantiomerenantiomer

BrBr

CHCH33 CCHH22CCHH33

HH CCHH22CCHH33

BrBr

CCHH33

HH HH

CCHH22CCHH33

BrBr

CCHH33

RR RR RR

Therefore: Therefore: TwoTwo exchanges exchanges leaveleave absolute absolute configuration. Example: (2configuration. Example: (2RR)-)-BromobutaneBromobutane

This procedure can be used to readily assign This procedure can be used to readily assign R,S R,S ::

Do Do doubledouble exchanges to place exchanges to place dd on on toptop..

Note: There are three possible arrangements for each, Note: There are three possible arrangements for each, RR or orSS,, e.g.,e.g., R R ::

cc

dd

bb

aa

bb

dd

cc aa

RR

BrBr

bb

dd

ccCHCH33 CHCH22CHCH33

HH

aa

bb

dd

cc

aa RR !! !!

Example:Example:

bb

dd

cc

aa

RRbb

dd

cc

aa

RR

Problem: Problem: Are these two molecules the same Are these two molecules the same or opposite enantiomers? or opposite enantiomers? RR or or SS ? ?

II

FF

HH CHCH33II

FF

HH

CHCH33

Solution:Solution:

II

FF

HH CHCH33

II

FF

HH

CHCH33

II

FF

HH CHCH33dd

aa

bb

cc

dd

aabb

cc

SS

II

FF

HH

CHCH33

aa

bb

cc

dd

dd

aa

bbccSS

Two Stereocenters:Two Stereocenters: The Chlorination of 2- The Chlorination of 2-BromobutaneBromobutane

**

BrBr BrBr

**

ClCl

**ClCl22, , hhνν-HCl-HCl

Generates: Generates:

RR, RS SR, SSRR, RS SR, SS

Four Four stereoisomersstereoisomers

RR SSRR SS and and RS SRRS SR are enantiomer are enantiomer pairspairs

DiastereomersDiastereomers are stereoisomers that are are stereoisomers that are not image-mirror-image-related. not image-mirror-image-related.

DiastereomersDiastereomers

I

C

BrCl

F

I

C

ClBrF

1

2

3

4

RR SS

BromochlorofluoroiodomethaneBromochlorofluoroiodomethane

1

32

4

Enantiomers

NUMBER OF NUMBER OF STEREOISOMERS POSSIBLESTEREOISOMERS POSSIBLE

How Many Stereoisomers How Many Stereoisomers Are Possible?Are Possible?

maximum number of stereoisomers = 2n,

where n = number of stereocenters(sterogenic carbons)

sometimes fewerthan this numberwill exist

CH3 C

CH2OH

CH3

CH2 CH CH

CH3

CH3

OH*

*

22 = 4 stereoisomers

R RR SS RS S

CH3

OH

CHCH3 CH3

***

23 = 8 stereoisomers

R R RR R SR S RS R R

R S SS R SS S RS S S

FINDING STEREOCENTERS FINDING STEREOCENTERS (STEREOGENIC CARBONS)(STEREOGENIC CARBONS)

plane( indicates no stereoisomers )

20 = 1 21 = 2 21 = 2

stereoisomers (max) :

O

CH3

O

CH3

O

CH3

**

O

CH3

CH3

O

CH3

CH3

O

CH3CH3

* ***

**

FINDING STEREOCENTERS FINDING STEREOCENTERS (STEREOGENIC CARBONS)(STEREOGENIC CARBONS)

plane( but only if cis )

22 = 4 22 = 4 22 = 4

stereoisomers (max) :

FINDING STEREOCENTERS (CHIRAL CARBONS)FINDING STEREOCENTERS (CHIRAL CARBONS)

CH3

CH3

HO

H

CH3

CH3

CH3

**

**

*

* *

*

n = 8

28 = 256

TYPES OF ISOMERSTYPES OF ISOMERS

CONSTITUTIONAL ISOMERS

Isomers with a differentorder of attachment ofthe atoms in their molecules

STEREOISOMERSIsomers with the same orderof attachment, but a differentconfiguration (3D arrangement)of groups on one or more of the atoms

ISOMERSDifferent compoundswith the same molecular formula

cis/trans ISOMERS

ENANTIOMERSStereoisomers whose molecules are non-superimposible mirrorimages of each other

DIASTEREOMERSStereoisomers whose molecules are not mirror images of each other

each isomer could

double bond or ring

both can apply

have stereoisomers

with a ring

TYPES OF ISOMERISMTYPES OF ISOMERISM(geometric)

MOLECULES WITH MOLECULES WITH TWO STEREOCENTERSTWO STEREOCENTERS

DIASTEREOMERS / MESO

22 = 4 stereoisomers possible

* *1234

HCH3CH3 H

ClBr

CH3 HH CH3

BrCl

HHCH3 CH3

BrCl

CH3CHCHCH3

ClBr

HHCH3 CH3

ClBr

2-Bromo-3-chlorobutane2-Bromo-3-chlorobutane

SRRS

SSRR

When comparing butanes, the comparisons are done best using the eclipsed conformation.

The relationships and planes of symmetry are not easily seen in other conformations.

H CH3

CH3 H

Cl Br

CH3 HH CH3

Br Cl

H HCH3 CH3

Br Cl

CH3CHCHCH3

Cl Br

H HCH3 CH3

Cl Br

enantiomers 1

enantiomers 2

diastereomers

S R RS

S S R R

mirror

2-Bromo-3-chlorobutane2-Bromo-3-chlorobutane

enantiomers-1

enantiomers-2

diastereomers

Models of the Isomers of 2-Bromo-3-chlorobutaneModels of the Isomers of 2-Bromo-3-chlorobutane

Br

Cl

CH3

H

(methyl groups are reduced to a single red atom)

H HCH3 CH3

Cl Cl

CH3CHCHCH3

Cl Cl

H HCH3 CH3

Cl Cl

CH3 HH CH3

Cl Cl

H CH3

CH3 H

Cl Cl

* *

2,3-Dichlorobutane2,3-Dichlorobutane

Now there is the possibility of a plane of symmetry.

The existence of a plane reduces the number of stereoisomers that are possible.

You will not find all 2n (= 4) stereoisomers.

C C

Cl Cl

H HCH3CH3

( Replace the Bromine with a second Chlorine )

(2n = 4)

H HCH3 CH3

Cl Cl

CH3CHCHCH3

Cl Cl

H HCH3 CH3

Cl Cl

CH3 HH CH3

Cl Cl

H CH3

CH3 H

Cl Cl

meso

enantiomers

diastereomers

S R

S S R R

mirror image is identical


H HCH3 CH3

Cl Cl

HCH3

Cl

HCH3

Cl

plane of symmetry

MESO ISOMERMESO ISOMER

S R

mirror

Meso isomer - has a plane of symmetry and the mirror image is identical to the original molecule.

meso

diastereomers

enantiomers

Cl

CH3

H

Models of the Isomers of 2,3-DichlorobutaneModels of the Isomers of 2,3-Dichlorobutane(methyl groups are reduced to a single red atom)

CONCLUSIONCONCLUSION

When a molecule has 1. multiple stereocenters and2. there is a possibility of an arrangement

with a plane of symmetry you will not always find all of the 2n stereoisomers that are possible.

Some of the stereoisomers may be meso isomers,and their mirror images will be superimposable(identical) - this will eliminate at least one of the possible stereoisomers, and sometimes more.

2n = the maximumnumber

PHYSICAL PROPERTIES OF PHYSICAL PROPERTIES OF ENANTIOMERS, DIASTEREOMERSENANTIOMERS, DIASTEREOMERS AND MESO COMPOUNDSAND MESO COMPOUNDS


W

CX

ZY

W

CXY

Z

(+)-nno (-)-nno


Enantiomers


REMEMBER :

IN CONTRAST :DIASTEREOMERS MAY HAVE DIFFERENT ROTATIONS

AND ALSO DIFFERENT PHYSICAL PROPERTIES

H COOHH

OHOH

HOOCHOOC HH COOH

OHOH

H HCOOH

OHOH

HOOC

meso

enantiomers

H COOHH

OHOH

HOOCHOOC HH COOH

OHOH

H HCOOH

OHOH

HOOC

meso

enantiomers(+)-tartaric acid (-)-tartaric acid

TARTARIC ACIDTARTARIC ACIDfrom fermentation of wine

meso -tartaric acid

Enantiomers

Diastereomers

HAS THREESTEREOISOMERS

TARTARIC ACIDTARTARIC ACID

(-) - tartaric acid (+) - tartaric acid

[]D = -12.0o []D = +12.0o

mp 168 - 170o mp 168 - 170o



d = 1.758 g/mL d = 1.758 g/mL

Enantiomers

meso - tartaric acid

mp 140o

d = 1.666 g/mL

solubility of 1 g 0.94 mL H2O

[]D = 0o

insoluble CHCl3

D

astereo

ers

i

m

CISCIS / / TRANSTRANS RINGS RINGS

DIASTEREOMERS

ClBr BrCl

Cl

Br Br

Cl

enantiomers

enantiomers

cis

trans

diastereomers

1-Bromo-2-chlorocyclopropane1-Bromo-2-chlorocyclopropanenote that the cis/trans isomers are also diastereomersnote that the cis/trans isomers are also diastereomers

R S SR

R R S S

BrBr BrBr

Br

Br Br

Br

mirror image identical

meso

enantiomers

diastereomers

1,2-Dibromocyclopropane1,2-Dibromocyclopropane

cis

trans

DISUBSTITUTED CYCLOHEXANESDISUBSTITUTED CYCLOHEXANES

USING PLANAR RINGS FOR STEREOCHEMICAL ANALYSIS

Br Cl BrCl

Cl

Br Br

Cl

1-Bromo-2-chlorocyclohexane1-Bromo-2-chlorocyclohexane

enantiomers

enantiomersdiastereomers

cis

trans

cyclohexanes may be analyzed using planar rings

Cl Cl ClCl

Cl

Cl Cl

Cl

1,2-dichlorocyclohexane1,2-dichlorocyclohexane

cis

trans

meso

enantiomers

diastereomers

mirror image identical

Cl Cl Cl Cl Cl Cl

cis (meso) trans (enantiomers)

DOT NOTATION CAN ALSO BE USEDDOT NOTATION CAN ALSO BE USED

plane of symmetryis readily seen

ClCl

Cl Cl Cl Cl Cl Cl1,1-dichloro

1,2-dichloro

cis trans

meso enantiomers

Cl

Cl

1,3-dichloro

cis trans

meso enantiomers

Cl

Cl

Cl

Cl

DOTS MAKE FIGURING CYCLIC ISOMERS EASYDOTS MAKE FIGURING CYCLIC ISOMERS EASYIsomers of Dichlorocyclohexane

1,4-dichloro

ClCl

ClCl

cis

trans both meso

INTERCHANGING GROUPSINTERCHANGING GROUPS

SOLVING A PROBLEM

INTERCHANGESINTERCHANGES

C

CH3

BrF

H

C

CH3

FBr

H

enantiomer

ONE STEREOCENTER

1..3..5…etc interchanges = enantiomer

2..4..6...etc interchanges = original compound

ODD:

EVEN:

C C

CH3

BrF

H CH3

H

FBr

PROBLEM: ARE THESE IDENTICALPROBLEM: ARE THESE IDENTICAL OR ARE THEY ENANTIOMERS?OR ARE THEY ENANTIOMERS?

C C C C

CH3

BrF

H CH3

Br

FH CH3

H

BrF

H

CH3 BrF

ENANTIOMER ENANTIOMERSAME

12

3

YOU CAN USEINTERCHANGES

AN EASIER WAY IS TO DETERMINE THE AN EASIER WAY IS TO DETERMINE THE ABSOLUTE CONFIGURATION OF EACH MOLECULEABSOLUTE CONFIGURATION OF EACH MOLECULE

C C

CH3

BrF

H CH3

H

FBr

Br

FCH3

H

R

TIP HYDROGENTIP HYDROGENBACKWARDSBACKWARDS

CH3

FBr

H

S

ENANTIOMERS

ROTATE TOROTATE TOTHE RIGHTTHE RIGHT

1

3

2 23

1

H HCH3 CH3

ClCl

CH3CHCHCH3

ClCl

H HCH3 CH3

ClCl

CH3 HH CH3

ClCl

H CH3CH3 H

ClCl

MORE THAN ONE STEREOCENTERMORE THAN ONE STEREOCENTER

To form an enantiomer you must interchange all of the stereocenters.

enantiomertwo stereocenterstwo interchanges

If a compound has more than one stereocenter,and you only interchange one of them, you will form a distereomer.

H HC H 3 C H 3

C l C l

C H 3 C H C H C H 3

C l C l

H HC H 3 C H 3

C l C l

C H 3 HH C H 3

C l C l

H C H 3

C H 3 H

C l C l

two stereocentersone interchange

diastereomer

HCH3

Cl

IF HYDROGEN IS NOT IN BACK - REVERSE YOUR RESULT !

REDUCTIO AD NUMERAE (reduce to a set of numbers)

F

1

23= S ( after reversal )

1

23

4

2

14

3

COPING TECHNIQUESCOPING TECHNIQUES

= S

twointerchanges

THERE IS NO SINGLE CORRECT METHODTO SOLVE A STEREOCHEMICAL PROBLEM

USE WHATEVER METHOD WORKS BEST FOR YOU

THERE ARE MANY METHODSTHERE ARE MANY METHODS THAT LEAD TO A SOLUTIONTHAT LEAD TO A SOLUTION

RELATIONSHIPSRELATIONSHIPSAMONG STEREOISOMERSAMONG STEREOISOMERS

Two Stereoisomers

Enantiomers

Diastereomers

not mirror images

nonsuperimposable mirror images

COMPARING TWO STEREOISOMERSCOMPARING TWO STEREOISOMERS

molecule has one or more stereocenters

has an enantiomer is meso

is chiral is achiral

mirror imagesuperimposes

no yes

plane of symmetry

optically active

optically inactive

no plane of symmetry

DETERMINING CHIRALITY / OPTICAL ACTIVITYDETERMINING CHIRALITY / OPTICAL ACTIVITY

FISCHER PROJECTIONSFISCHER PROJECTIONS

CHO

HOCH2 HOH

OHH

CHO

CH2OHH

CH2OH

CHO

OH

EVOLUTION OF THEEVOLUTION OF THEFISCHER PROJECTIONFISCHER PROJECTION

Substituents willstick out towardyou like prongs

Fischer Projection

Main chain bendsaway from you

“Sawhorse” Projection

Orient themain chainvertically withthe mostoxidized groupat the top.

ORIENTATION OFTHE MAIN CHAINAND THE SUBSTITUENTSIN A FISCHERPROJECTION

continuation of the main chain

CH3

OHH

OHH

OHH

CH3

OH

OH

OH

H

H

H

CH3 CH2OH CH

C

OH

O

CHO COOH

CO

HC

O

OH

INCREASING OXIDATION STATEINCREASING OXIDATION STATE

increasing oxidation state

In the Fisher projection the main chain is orientedwith the most highly oxidized group at the top.

C=O on carbon-2 increasesthe priority of C-OH

H HCH3 CH3

Cl Br

CH3

CH3

H

H

Cl

Br

Cl

CH3

Br

CH3

main chain in red

orient main chain vertically

convert toFischerProjection

rotate 90o

Br

Cl

CH3

H

H

CHO

OH

OH

CH2OH

CHO

HO

HO

CH2OH

CHO

OH

OH

CH2OH

CH2OH

HO

HO

CH3

Mirror images (enantiomers)are created by switching substituents to the other side.

This is equivalent to turningthe molecule over like apancake.

OPERATIONS WITH FISCHER PROJECTIONSOPERATIONS WITH FISCHER PROJECTIONS

All stereocenters must beswitched to get an enantiomer (the mirror inverts them all).

CHO

OH

HO

CH2OH

diastereomers

enantiomers

If you switch only some of the stereocenters,not all of them, you get a diastereomer.

Rotation by 180o in the planeof the paper does not changethe molecule.

No other angle of rotationis allowed.

180o

OPERATIONS WITH FISCHER PROJECTIONSOPERATIONS WITH FISCHER PROJECTIONS

CHO

OH

OH

CH2OH

CH2OH

HO

HO

CHO

.

Rotation can be used for comparisons …..

3

A

Does A have an enantiomer A* ?

CH3

Br

Br

CH

CH

1) reflect

A* 3

Br

Br

CH3

HC

2) rotate

3

Br

Br

CH3

3) compare

NO !

CH3

Br

Br

CH3

A The molecule did not have an enantiomer because itwas not chiral.

It had a plane of symmetry,rendering it a meso molecule.

THE MOLECULE WAS MESO !THE MOLECULE WAS MESO !

plane of symmetry

CHO

OH

HO

OH

HO

CH2OH

CHO

OH

OH

OH

OH

CH2OH

CHO

HO

HO

HO

HO

CH2OH

CHO

HO

OH

OH

OH

CH2OH

CHO

OH

HO

HO

OH

CH2OH

CHO

OH

OH

HO

OH

CH2OH

CHO

OH

OH

OH

HO

CH2OH

CHO

HO

HO

OH

OH

CH2OH

CHO

OH

HO

OH

OH

CH2OH

ENANTIOMERSENANTIOMERS

DIASTEROMERSDIASTEROMERS

all stereocentershave been inverted

only some stereocentershave been inverted

HOME STUDYCan you find all 16(2n = 16) stereo-isomers? Group them as pairs ofenantiomers. Donot repeat any!

COOH

OH

OH

OH

OH

COOH

FURTHER HOME STUDY

Find all of the stereoisomers for this compound. Group allenantiomers in pairs. Are there any meso stereoisomers?

Will you find 16 (24 = 16)stereoisomers? Why orwhy not?

DETERMINATION OF DETERMINATION OF R / S CONFIGURATIONR / S CONFIGURATIONIN FISCHER PROJECTIONSIN FISCHER PROJECTIONS

H

CH2OH

CHO

OH

PLACE THE PRIORITY=4 GROUP IN ONE OF THE VERTICALPOSITIONS, THEN LOOK AT THE OTHER THREE

H

OH

OHC CH2OH1

2

3

4

1

2 3

4

R

alternatively:

H

CH2OH

CHO

OH1

2

3

4 HOCH2 CHO

OH2

1

4

3

H

R

#4 at top position

#4 at bottom position

BOTH IN BACKSAME RESULT

H

CH2OH

CHO

OH 1

2

3

4

FOR THE MENTALLY AGILEFOR THE MENTALLY AGILEWHY BOTHER INTERCHANGING? JUST REVERSE YOUR RESULT!

H comingtoward you

Same moleculeas on previousslide. S reverse R

Same resultas before.

CH2OH

CH2OH

H

CHO

OH1

2

3

4

H

CH2OH

CHO1

2

3

4

HO

CYCLIC ROTATION OF GROUPS IN A CYCLIC ROTATION OF GROUPS IN A FISCHER PROJECTIONFISCHER PROJECTIONYOU MAY FIX ONE GROUP AND THEN ROTATE THE OTHER THREE

H

CHO

OH1

3

4

2

Any of the fourgroups may be fixed.

This rotation does notchange the molecule.

R configurationfixed

fixed

rotate

OTHER EXAMPLESOTHER EXAMPLES

diastereomers

3- Chloro-2-butanol3- Chloro-2-butanol

OH

CH3

Cl

CH3

HO

CH3

Cl

CH3

HO

CH3

Cl

CH3

OH

CH3

Cl

CH3

enantiomers-1 enantiomers-2


meso

diastereomers

Cl

CH3

Cl

CH3

Cl

CH3

Cl

CH3

Cl

CH3

Cl

CH3

Cl

CH3

Cl

CH3

enantiomers

STEREOCENTERS OTHER THANSTEREOCENTERS OTHER THAN STEREOGENIC CARBONSTEREOGENIC CARBON

STEREOGENIC CARBONS are not the only possible stereocenters in a molecule.

TETRAHEDRAL ATOMSTETRAHEDRAL ATOMSNON-CARBON STEREOCENTERSNON-CARBON STEREOCENTERS

Any atom which is tetrahedral with four differentgroups has the potential to be stereogenic.

CH3

Si H

CH2CH3

CH3

P H

CH2CH3

+N

CH2CH3

CH2CH2CH3

CH3+

PYRIMIDAL ATOMS WITH AN PYRIMIDAL ATOMS WITH AN UNSHARED PAIRUNSHARED PAIR

P

CH2CH3

CH3

.. ..N

CH2CH3

CH2PhCH3

....S

F

ClO- +

If the atoms do not invert (see next slide) thesemolecules will be chiral.

Pyrimidal atoms can be stereocenters.

N

H

CH2CH3CH3

..

..

N

CH2CH3HCH3

..

INVERSION OF SMALL AMINES INVERSION OF SMALL AMINES

Small amines (those with H, CH3, or CH2CH3 groups) exhibit fast inversion rates:

INVERSION OF SMALL AMINES INVERSION OF SMALL AMINES

With larger groups, the rate of inversion slows.

If fast inversion occurs, a pyrimidal nitrogen will not be an active stereocenter.

..

N

CH3CH2

H CH3

..

..N

HCH2CH3CH3

..

When there is no inversion, an amine with three different groups attached will be a stereocenter.

SR RACEMIC MIXTURE

OF ENANTIOMERS

If the groups are large enough, inversion stops completely.

: = priority 4

In acid solution, fast inversion may occur if one of the attached groups is a hydrogen atom (H).

A CHIRAL AMINE IN ACID SOLUTIONA CHIRAL AMINE IN ACID SOLUTION

..N

CH2CH2CH3

H

..

....N

CH2CH2CH3

H

H+H+

HCH2CH2CH3N

-H+

Removal of a different hydrogen (blue) from the ammonium ion than the one added (red), causes a change (inversion)of configuration.

+

amine 1 ammonium ion amine 2

PROTON EXCHANGE

SS

RR

BICYCLIC AMINES ARE USUALLY RIGID BICYCLIC AMINES ARE USUALLY RIGID ..... and they do not invert

The nitrogen is rigidly held inthe bicyclic rings and cannotinvert.

N

NTröger’s base

[]D = 287o

The rings cannot invert.

NCH3

..

CH3

H

*

* *

*

*

*

NOTE: Without the exo methyl groupthere would be a plane of symmetryand the molecule would be meso.

AZIRIDINES DO NOT INVERTAZIRIDINES DO NOT INVERT

Aziridine = a three-membered ring containing a nitrogen atom.

NCH3O

CH3

H

..N

CH3

H

OCH3

:

trans cis

This amine does not invert even at 200o

The transition state would be planar, requiring a 120o angle.

diastereomers

**

*

*

STEREOCENTERS THAT DO NOTSTEREOCENTERS THAT DO NOTINVOLVE A STEREOGENIC ATOMINVOLVE A STEREOGENIC ATOM

NOT ALL STEREOCENTERS ARE ATOMSNOT ALL STEREOCENTERS ARE ATOMS

Sometimes a group of atoms (none of which is astereocenter itself) can confer chirality.

C C CH

CH3Cl

FC C C

H

H3CCl

F

The allene group (C=C=C) is a stereocenter. An allene is chiral when four different groups areattached ..... try it with any two groups the same!

Also notice that this group is a stereocenter, andit has no stereogenic (chiral) carbon atoms.

remember thatan allene has atwist in the center

C C CH

C H 3C l

FC C C

H

H 3 CC l

FC C C

H

C H 3C l

FC C C

H

H 3 CC l

FC C C

H

C H 3C l

FC C C

H

H 3 CC l

FC C C

H

C H 3C l

FC C C

H

H 3 CC l

F

The allene group is just like a stretched outtetrahedral carbon.

remember thetwist

COMPARISON OF THE ALLENE AND COMPARISON OF THE ALLENE AND STEREOGENIC CARBON STEREOCENTERSSTEREOGENIC CARBON STEREOCENTERS

both ends areperpendicular

SPIRO COMPOUNDS CAN ALSO BE CHIRALSPIRO COMPOUNDS CAN ALSO BE CHIRAL

FCl

CH3

H H

H3C

ClF

CH3

HCl

F H3C

H Cl

F

enantiomers

enantiomers

C H 3

HC l

F H 3 C

H C l

F

HEPTIHELICENEHEPTIHELICENE

coronene heptihelicene(completely planar)

(makes a helix which is chiral)heptihelicene has an enantiomer

has no enantiomer

has no stereocenters - all sp2 atoms

seven ringsoverlapcompare:

helices may be right- or left-handed

six rings joinperfectly

H

H

H

H

transtrans - CYCLOOCTENE - CYCLOOCTENE

This molecule has no stereocenters,but it is chiral.

enantiomers

( Remember that this is the smallest ring which can contain a trans double bond.)

The enantiomers have either a right-handed or a left-handed twist.

SUMMARYSUMMARY

It doesn’t even matter whether there are any other stereocenters present that we recognize as the usual sources of chirality (including allenes, spiro rings, etc.)

The entire molecule can be chiral (it can be its own stereocenter).

Stereogenic Carbon Atoms (or P, or N, or S atoms) are not required to be present for a molecule to be chiral !

THERE IS NO REQUIREMENT FOR ATOMICTHERE IS NO REQUIREMENT FOR ATOMICSTEREOCENTERS FOR A MOLECULE TO BE CHIRALSTEREOCENTERS FOR A MOLECULE TO BE CHIRAL

A chiral molecule needs only to have no symmetry of any kind.

The only definitive test for chirality is to take the mirror image of the molecule and check if it willsuperimpose :

chiral = mirror image doesnt superimposeachiral = mirror image does superimpose

It doesn’t matter if you recognize any stereocentersor not ! The entire molecule can be chiral !

TESTING FOR CHIRALITYTESTING FOR CHIRALITY

A compound can have stereocenters and not be chiral.

meso compounds are an example

BrBr

CH3

CH3

HH

COOH

OH

OH

COOH

STEREOCENTERS give a molecule the possibility of being chiral, but they do not assure it; a plane of symmetry is possible.

NOTE ALSO THATNOTE ALSO THAT

S

RR

S

The handedness of the chiral herbicide metolachlor.The handedness of the chiral herbicide metolachlor.

Enantiomers and Physiological Activity

Drugs: Enantiomers Act Very Differently

H2NOH

O

O

H2N H

S

Bitter Sweet

Asparagine

NH2

HO

O

O

NH2H

R

Cl

Cl

OOH

O

CH3H

R

Cl

Cl

OHO

O

H3C H

S

Active Inactive

Dichlorprop

(Herbicide)

HO

HOH2CHN

HO H

OH

CH2OHHN

OHH

RS

BronchodilatorAntagonist

Albuterol

Enantiomer Recognition

In nature: Enzymes, receptorsIn nature: Enzymes, receptors

Synthetic: Enantiomerically pure reagents and catalystsSynthetic: Enantiomerically pure reagents and catalysts

Enantioselectivity:Generating One Enantiomer from

Achiral Material

A A “handed” “handed” reagentreagentor catalyst can or catalyst can telltellthe differencethe difference

Which?Which?

Nevertheless, we still Nevertheless, we still need a chiral auxiliaryneed a chiral auxiliary to generate to generate a new stereocenter selectively. What generated the a new stereocenter selectively. What generated the “first” enantiomer?“first” enantiomer?

Amplification of Chirality from Extremely Low to Greater than 99.5% ee by Asymmetric AutocatalysisItaru Sato, Hiroki Urabe, Saori Ishiguro,Takanori Shibata, and Kenso Soai*

Angew. Chem. Int. Ed. 2003, 42, 315

Documents

Stereo Chemistry